West Nile Virus (“WNV”) is in the family Flaviviridae. Infection is usually contracted through a mosquito vector transferred through the insect's bite. West Nile infects all types of animals and birds across the globe. This virus was first discovered in the North American region in 1999 with the first diagnosis occurring in Canadian horses. Presently, West Nile Virus has become endemic in the United States affecting birds, humans, and animals of all types. In 2002, over 14,700 confirmed cases of West Nile Virus were reported in 43 states.
The spread of WNV has been influenced by several factors. Since the mosquito is the vector for the virus and perpetuates WNV, the ecological conditions conducive to growth and development of mosquito populations have had an impact of the spread of the WNV. There are several tactics that have been utilized to control populations of mosquitoes in an effort to prevent the spread of WNV. These tactics include the use of pesticides, repellants, physical barriers preventing contact between mosquitoes and animals, eliminating environments that perpetuate breeding of mosquitoes, and the use of immunizations. Typical signs of WNV include various symptoms affecting the central nervous system. Symptoms of encephalitis are often seen and include viremia, histopathologic lesions of the central nervous system, anorexia, depression, fever, weakness, abnormal gait, paralysis of hind limbs, impaired vision, ataxia, aimless wandering, convulsions, inability to swallow, coma, and death.
A few vaccines directed towards WNV have been introduced which are undesirable for various reasons. For example, one vaccine was produced from a canarypox-vectored West Nile Virus. Another set of vaccines were produced from a recombinant chimeric protein of West Nile Virus, wherein the chimeric protein vaccine was designed by fusing a modified version of bacterial flagellin (STF2 Delta) to the EIII domain of the WNV envelope protein. Another vaccine included an inactivated early North American West Nile strain that required a metabolizable oil as an adjuvant. Finally, a live, attenuated chimeric vaccine was produced from an infectious clone of yellow fever 17D virus in which the pre-membrane and envelope proteins have been replaced by the corresponding genes of WN(4).
There are several problems inherent in vaccines described above. Vaccines containing live viral organisms have the risk of infecting an animal with the virus through vaccination leading to sickness and even death. Chimeric protein vaccines, recombinantly expressed vaccines, and some subunit vaccines have the problem of limited immunological activity and effect related to the number of proteins included in the vaccine composition. The efficacy of these types of vaccines is usually limited and the risk of infection by the virus or reversion to wild type virus is prevalent. In addition, some of the adjuvants utilized in common vaccines are comprised of metabolizable oils which are removed relatively rapidly from the body and limit the duration during which the immune system of the vaccinated animal may respond to the immunogenically active composition. Other adjuvants can cause allergic reactions and unfavorable effects in the vaccinated animals. Additionally, these vaccines do not include antigens for stimulating immunity to other pathogens besides WNV, so they fail to protect animals against several diseases with both convenience and safety. Also, all previous vaccines were derived from an early isolate of WNV that is no longer present in the environment, and hence, can no longer infect animals and cause disease.
Accordingly, what is needed in the art is a vaccine that is safe for administration to animals of all ages, including pregnant animals, that includes adjuvants suitable for aiding the immunogenic effect and duration of the vaccine, and that is prepared from contemporary or dominant isolates of WNV that remain present in the natural environment and cause disease against which such vaccines would afford protection. What is further needed is a vaccine that reduces the incidence and/or severity of up to and including the elimination or prevention of clinical signs associated with the disease or infection by West Nile Virus. Additionally what is needed is a vaccine against West Nile virus, which includes West Nile Virus antigens in combination with antigens from other equine pathogens, thereby providing further protection by reducing the incidence of or severity of clinical signs of disease from both West Nile Virus and the other pathogen(s).